A conserved ion channel function of STING mediates noncanonical autophagy and cell death.

ABSTRACT: The cGAS/STING pathway triggers inflammation upon diverse cellular stresses such as infection, cellular damage, aging, and diseases. STING also triggers noncanonical autophagy, involving LC3 lipidation on STING vesicles through the V-ATPase-ATG16L1 axis, as well as induces cell death. Although the proton pump V-ATPase senses organelle deacidification in other contexts, it is unclear how STING activates V-ATPase for noncanonical autophagy. Here we report a conserved channel function of STING in proton efflux and vesicle deacidification. STING activation induces an electron-sparse pore in its transmembrane domain, which mediates proton flux in vitro and the deacidification of post-Golgi STING vesicles in cells. A chemical ligand of STING, C53, which binds to and blocks its channel, strongly

SUBMITTER: Xun J 

PROVIDER: S-EPMC10897221 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature